The influence of
cancer cachexia and
chemotherapy and subsequent recovery of skeletal muscle
protein mass and turnover was investigated in mice.
Cancer cachexia was induced using colon 26
adenocarcinoma, which is characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea,
cystemustine (C(6)H(12)CIN(3)O(4)S). Reduced food intake was not
a factor in these studies. Three days after
cachexia began, healthy and
tumor-bearing mice were given a single
intraperitoneal injection of
cystemustine (20 mg/kg). Skeletal muscle mass in
tumor-bearing mice was 41% lower (P < 0.05) than in healthy mice 2 wk after
cachexia began. Skeletal muscle wasting was mediated initially by decreased
protein synthesis (-38%; P < 0.05) and increased degradation (+131%; P < 0.05); later wasting resulted solely from decreased synthesis (~-54 to -69%; P < 0.05). Acute cytotoxicity of
chemotherapy did not appear to have an important effect on skeletal muscle
protein metabolism in either healthy or
tumor-bearing mice. Recovery began 2 days
after treatment; skeletal muscle mass was only 11% lower than in healthy mice 11 days after
chemotherapy. Recovery of skeletal muscle mass was affected initially by decreased protein degradation (-80%; P < 0.05) and later by increased
protein synthesis (+46 to +73%; P < 0.05) in cured compared with healthy mice. This study showed that skeletal muscle wasted from
cancer cachexia and after chemotherapeutic treatment is able to generate a strong anabolic response by making powerful changes to
protein synthesis and degradation.